A Multicentre, Randomised, Double-blind, Placebo-controlled, Phase 2 Study Evaluating the Efficacy and Safety of Anifrolumab in Adult Subjects With Active Proliferative Lupus Nephritis
Overview
- Phase
- Phase 2
- Intervention
- Anifrolumab
- Conditions
- Lupus Nephritis
- Sponsor
- AstraZeneca
- Enrollment
- 147
- Locations
- 1
- Primary Endpoint
- Change From Baseline in 24-hour Urine Protein to Creatinine Ratio (UPCR)
- Status
- Completed
- Last Updated
- 4 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the efficacy and safety of an intravenous treatment regimen of two doses of anifrolumab versus placebo in adult subjects with active proliferative lupus nephritis (LN).
Detailed Description
This is a Phase 2, multicentre, multinational, randomised, double-blind, placebo-controlled study to evaluate the efficacy and safety of two intravenous (IV) treatment regimens of anifrolumab versus placebo while taking standard of care (SOC) treatment with mycophenolate mofetil (MMF) and corticosteroids in adult subjects with active proliferative lupus nephritis (LN).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Age 18 through 70 years at the time of screening
- •Fulfils at least 4 of the 11 criteria of the revised 1982 ACR classification criteria for SLE, at least one of which must be:
- •Positive antinuclear antibody (ANA) test (1:40 or higher) or
- •Elevated anti-dsDNA antibodies at screening (reported as equivocal or positive results), as per the centrallaboratory; or
- •Anti-Smith antibody at screening elevated to above normal (ie, positive or equivocal results) as per the central laboratory
- •Class III (±Class V) or Class IV (±Class V) LN according to the World Health Organisation (WHO) or 2003 ISN/RPS classification based on a renal biopsy obtained within 12 weeks prior to signing the ICF or during the screening period:
- •Urine protein to creatinine ratio \>1 gm/gm (113.17 mg/mmol), obtained on a 24-hour urine collection at screening
- •Estimated glomerular filtration rate ≥35 mL/min/1.73 m2
- •Must not have active or latent TB on either chest radiograph or by Quantiferon gold test
- •Women of childbearing potential must have a negative serum beta-hCG test at screening and negative urine pregnancy test prior to the first dose of sponsor-provided MMF.
Exclusion Criteria
- •Receipt of any investigational product (small molecule or biologic) or commercially available biologic agent within four weeks or 5 half lives prior to signing of the ICF, whichever is greater
- •Pure Class V membranous LN on a renal biopsy obtained within 12 weeks prior to signing ICF or during the screening period
- •Known intolerance to ≤1.0 gm/day of MMF
- •History of dialysis within 12 months prior to signing the ICF or expected need for renal replacement therapy (dialysis or renal transplant) within a 6 month period after enrolment
- •Subjects, who at the time of signing the ICF, received any of the following immunosuppressive therapies after their qualifying biopsy
- •Oral corticosteroids \>0.5 mg/kg/day for more than 8 weeks or
- •Oral or IV pulse methylprednisolone \>3.0 gm (cumulative dose) or
- •IV cyclophosphamide \>2 pulses of high-dose (≥0.5 gm/m2) or \>4 doses of low dose (500 mg every 2 weeks) or
- •Average MMF \>2.5 gm/day (\>1800 mg/day of enteric-coated mycophenolate sodium) for more than 8 weeks or
- •Tacrolimus \>4 mg/day for more than 8 weeks
Arms & Interventions
Anifrolumab - Lower Dose
Anifrolumab - Lower Dose
Intervention: Anifrolumab
Anifrolumab - Higher Dose
Anifrolumab - Higher Dose
Intervention: Anifrolumab
Placebo
Placebo IV Q4W plus SOC
Intervention: Placebo
Outcomes
Primary Outcomes
Change From Baseline in 24-hour Urine Protein to Creatinine Ratio (UPCR)
Time Frame: From Week 1 (Baseline) up to Week 52
To evaluate the efficacy of anifrolumab plus SOC (combination of mycophenolate mofetil and corticosteroids) compared with placebo plus SOC in subjects with active proliferative lupus nephritis (LN). Geometric mean ratio of 24-hour UPCR at week 52 over baseline. Values \<1 indicate improvement from baseline.
Secondary Outcomes
- Proportion of Subjects Achieving the Composite Endpoint Complete Renal Response (CRR)(Week 52)